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WO2010139669A1 - Module médicamenteux avec médicament pré-mélangé - Google Patents

Module médicamenteux avec médicament pré-mélangé Download PDF

Info

Publication number
WO2010139669A1
WO2010139669A1 PCT/EP2010/057576 EP2010057576W WO2010139669A1 WO 2010139669 A1 WO2010139669 A1 WO 2010139669A1 EP 2010057576 W EP2010057576 W EP 2010057576W WO 2010139669 A1 WO2010139669 A1 WO 2010139669A1
Authority
WO
WIPO (PCT)
Prior art keywords
reservoir
medicament
drug
dose
needle
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2010/057576
Other languages
English (en)
Inventor
Michael James David Heald
Christopher James Smith
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi Aventis Deutschland GmbH
Original Assignee
Sanofi Aventis Deutschland GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanofi Aventis Deutschland GmbH filed Critical Sanofi Aventis Deutschland GmbH
Priority to BRPI1012572A priority Critical patent/BRPI1012572A2/pt
Priority to CA2763506A priority patent/CA2763506A1/fr
Priority to EP10720172A priority patent/EP2437809A1/fr
Priority to JP2012513582A priority patent/JP5887263B2/ja
Priority to US13/375,720 priority patent/US9089648B2/en
Priority to CN201080032168.0A priority patent/CN102458519B/zh
Priority to AU2010255755A priority patent/AU2010255755B2/en
Publication of WO2010139669A1 publication Critical patent/WO2010139669A1/fr
Priority to IL216571A priority patent/IL216571A/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/24—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic
    • A61M5/2448—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic comprising means for injection of two or more media, e.g. by mixing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/24—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic
    • A61M5/2455—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic with sealing means to be broken or opened
    • A61M5/2466—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic with sealing means to be broken or opened by piercing without internal pressure increase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
    • A61M5/3294—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles comprising means for injection of two or more media, e.g. by mixing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M2005/1787—Syringes for sequential delivery of fluids, e.g. first medicament and then flushing liquid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2206/00—Characteristics of a physical parameter; associated device therefor
    • A61M2206/10—Flow characteristics
    • A61M2206/20—Flow characteristics having means for promoting or enhancing the flow, actively or passively
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31525—Dosing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31565—Administration mechanisms, i.e. constructional features, modes of administering a dose
    • A61M5/31566—Means improving security or handling thereof
    • A61M5/31573—Accuracy improving means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
    • A61M5/34—Constructions for connecting the needle, e.g. to syringe nozzle or needle hub
    • A61M5/347—Constructions for connecting the needle, e.g. to syringe nozzle or needle hub rotatable, e.g. bayonet or screw

Definitions

  • This disclosure relates to medical devices and methods of delivering at least two drug agents from separate reservoirs using devices having only a single dispense interface.
  • a single delivery procedure initiated by the user causes a non-user settable dose of a second drug agent and a variable set dose of a first drug agent to be delivered to the patient.
  • Our invention is specifically directed to a medicated module having a premix of at least two drug agents, where one of the drug agents is the same as found in an attached drug delivery device.
  • Our invention is of particular benefit where the therapeutic response can be optimized for a specific target patient group, through control and definition of the therapeutic profile.
  • Certain disease states require treatment using one or more different medicaments.
  • Some drug compounds need to be delivered in a specific relationship with each other in order to deliver the optimum therapeutic dose.
  • combination therapy may be desirable, but not possible in a single formulation for reasons such as, but not limited to, stability, compromised therapeutic performance and toxicology.
  • GLP-1 glucagon-like peptide-1
  • GLP-1 glucagon-like peptide-1
  • the two or more active agents may interact with each other during the long-term, shelf life storage of the formulation.
  • a further problem is that the quantities and/or proportions of each active agent making up the combination therapy may need to be varied for each user or at different stages of their therapy. For example one or more active agents may require a titration period to gradually introduce a patient to a "maintenance" dose. A further example would be if one active agent requires a non-adjustable fixed dose while the other is varied in response to a patient's symptoms or physical condition. This problem means that pre-mixed formulations of multiple active agents may not be suitable as these pre-mixed formulations would have a fixed ratio of the active components, which could not be varied by the healthcare professional or user.
  • medicated module is preferably used to characterize a containment or reservoir of a (secondary) drug compound within a needle sub- assembly.
  • a medicated module may comprise at least one double ended needle.
  • a medicated module may comprise a needle guard and/or a bypass.
  • the bypass can be any configuration, such as, a channel, pipe, conduit, groove, slot, or any other like pathway that is capable of carrying the medicament from the primary reservoir (e.g. cartridge) to the second needle or output needle without communicating with the secondary reservoir/medicament
  • the volume of the secondary medicament in the reservoir will offset the absolute volume of the actual dose of the primary medicament that is delivered from the delivery device.
  • a given volume or set dose of medicament can contain a variety of concentrations of one or more drug agents depending on the formulation protocol that was used to prepare the medicament.
  • C amount of primary medicament volume A minus the volume B of reservoir
  • a complex technical redesign of the delivery device would be required to deliver the complete dose A and also to indicate the correct quantity or concentration of delivered primary medicament to the user in all use scenarios (e.g.
  • the general problem to be solved by the present invention is to provide a medicated module, a drug delivery system and a method where the administration of a medicament is facilitated.
  • the disclosed medicated module allows complex combinations of multiple drug compounds within a single drug delivery system.
  • a user may be enabled to set and dispense a multi-drug compound device through one single dose setting mechanism and a single dispense interface.
  • This single dose setter may control the mechanism of the device such that a predefined combination of the individual drug compounds is delivered when a single dose of one of the medicaments is set and dispensed through the single dispense interface.
  • the term drug dispense interface preferably is, in the context of this disclosure, any type of outlet that allows the two or more medicaments to exit the drug delivery system and be delivered to the patient.
  • the single drug dispense interface comprises a hollow needle cannula.
  • this invention may be of particular benefit to users with dexterity or computational difficulties as the single input and associated predefined therapeutic profile removes the need for them to calculate their prescribed dose every time they use the device and the single input allows considerably easier setting and dispensing of the combined compounds.
  • Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin.
  • Gonadotropine Follitropin, Lutropin, Choriongonadotropin, Menotropin
  • Somatropine Somatropin
  • Desmopressin Terlipressin
  • Gonadorelin Triptorelin
  • Leuprorelin Buserelin
  • Nafarelin Goserelin.
  • a further particular benefit of the disclosed medicated module may be that it makes it possible to tailor dose regimes when required, especially where a titration period is necessary for a particular drug.
  • the medicated module could be supplied in a number of titration levels with obvious differentiation features such as, but not limited to, aesthetic design of features or graphics, numbering etc, so that a user could be instructed to use the supplied medicated module in a specific order to facilitate titration.
  • the prescribing physician may provide the patient with a number of "level one" titration medicated modules and then when these were finished, the physician could then prescribe the next level.
  • a key advantage of this titration program is that the primary device remains constant throughout.
  • a drug delivery device preferably comprises a primary reservoir of medicament containing at least one drug agent, a dose setter, a dose button, and a delivery mechanism.
  • the dose button is operably connected to the primary reservoir.
  • the dose setter is operably connected to the primary reservoir.
  • the delivery mechanism may be of any type, e.g. the drive mechanism may utilize a rotatable piston rod, preferably a rotatable piston rod with two distinct threads.
  • One alternative is to have the assembly/filling process set up so as to ensure that a "plug" of gas (e.g. air or an inert gas, such as nitrogen) is present in the upper section 6 of the needle (above the enlarged section 5) this may act to ensure that the first and second medicaments are kept separate from each other thereby help ensure sequential delivery by action of a virtual piston created by the plug of air.
  • This plug may additionally help ensure that there is no opportunity for the primary and secondary medicaments to mix prior to dispense (i.e. if the medicated module is left in the attached position for an extended period of time prior to the injection action being undertaken.
  • FIG. 2 Another embodiment of our invention is shown in Fig. 2 where a primary needle 15pierces the septum 10 of the device cartridge 11 and a second needle 16 is used to subcutaneously inject the medicament. Located between the two needles is a recess 17 containing the secondary reservoir of the second medicament 2. The primary needle 15 is attached to a retention cap 18, which when inserted into the top of the recess 17 provides a fluid seal.

Landscapes

  • Health & Medical Sciences (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Abstract

L'invention porte sur un module médicamenteux (4) pour un système d'injection destiné à co-administrer au moins deux médicaments (1, 2), dans lequel un dispositif d'administration primaire (7) contient un premier agent de médicament et accepte un module médicamenteux (4) contenant une seule dose d'un médicament secondaire pré-mélangé (2) contenant le premier agent de médicament et au moins un second agent de médicament, le médicament primaire (1) et le médicament secondaire pré-mélangé secondaire (2) étant tous deux administrés par une aiguille creuse unique (3, 16, 21, 31).
PCT/EP2010/057576 2009-06-02 2010-06-01 Module médicamenteux avec médicament pré-mélangé Ceased WO2010139669A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
BRPI1012572A BRPI1012572A2 (pt) 2009-06-02 2010-06-01 módulo medicinal com medicamento pré-misto
CA2763506A CA2763506A1 (fr) 2009-06-02 2010-06-01 Module medicamenteux avec medicament pre-melange
EP10720172A EP2437809A1 (fr) 2009-06-02 2010-06-01 Module médicamenteux avec médicament pré-mélangé
JP2012513582A JP5887263B2 (ja) 2009-06-02 2010-06-01 プレミックス薬剤による薬用モジュール
US13/375,720 US9089648B2 (en) 2009-06-02 2010-06-01 Medicated module with premix medicament
CN201080032168.0A CN102458519B (zh) 2009-06-02 2010-06-01 具有预混药剂的加药模块
AU2010255755A AU2010255755B2 (en) 2009-06-02 2010-06-01 Medicated module with premix medicament
IL216571A IL216571A (en) 2009-06-02 2011-11-23 Component for treatment with pre-mixed medication

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US18346309P 2009-06-02 2009-06-02
US61/183,463 2009-06-02
EP09009659.5 2009-07-25
EP09009659 2009-07-25

Publications (1)

Publication Number Publication Date
WO2010139669A1 true WO2010139669A1 (fr) 2010-12-09

Family

ID=41259097

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2010/057576 Ceased WO2010139669A1 (fr) 2009-06-02 2010-06-01 Module médicamenteux avec médicament pré-mélangé

Country Status (11)

Country Link
US (1) US9089648B2 (fr)
EP (1) EP2437809A1 (fr)
JP (1) JP5887263B2 (fr)
CN (1) CN102458519B (fr)
AR (1) AR076716A1 (fr)
AU (1) AU2010255755B2 (fr)
BR (1) BRPI1012572A2 (fr)
CA (1) CA2763506A1 (fr)
IL (1) IL216571A (fr)
TW (1) TW201103594A (fr)
WO (1) WO2010139669A1 (fr)

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JP2014502871A (ja) * 2010-12-21 2014-02-06 サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング 薬物送達デバイス用のカートリッジホルダアセンブリ
CN103582473A (zh) * 2011-01-10 2014-02-12 拜昂·塞翁·常 紧凑药物复原装置和方法
WO2014149357A1 (fr) * 2013-03-22 2014-09-25 Amgen Inc. Injecteur et procédé d'assemblage
WO2015061386A1 (fr) * 2013-10-24 2015-04-30 Amgen Inc. Injecteur et procédé d'assemblage
US9174002B2 (en) 2004-12-30 2015-11-03 Byeong S. Chang Method for storing and delivering a drug
CN106474598A (zh) * 2011-04-28 2017-03-08 赛诺菲-安万特德国有限公司 用于医疗装置的阀配置
US9919108B2 (en) 2011-08-30 2018-03-20 Novo Nordisk A/S Arrangement for sequential delivery of fluid volumes
EP3191068A4 (fr) * 2014-09-09 2018-05-30 Byeong Seon Chang Dispositif et procédé de distribution de solution
US9987428B2 (en) 2011-10-14 2018-06-05 Amgen Inc. Injector and method of assembly
WO2019211858A1 (fr) * 2018-05-04 2019-11-07 Sealantis Ltd. Système de reconstitution et de mélange

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ES2314182T3 (es) 2002-02-11 2009-03-16 Antares Pharma, Inc. Inyector intradermico.
HUE042286T2 (hu) 2005-01-24 2019-06-28 Antares Pharma Inc Tûvel szerelt, elõre töltött belövõ fecskendõ
US9144648B2 (en) 2006-05-03 2015-09-29 Antares Pharma, Inc. Injector with adjustable dosing
WO2007131013A1 (fr) 2006-05-03 2007-11-15 Antares Pharma, Inc. Injecteur de reconstitution à deux étages
CA2718053C (fr) 2008-03-10 2016-09-27 Antares Pharma, Inc. Dispositif de securite pour injecteur
US8376993B2 (en) 2008-08-05 2013-02-19 Antares Pharma, Inc. Multiple dosage injector
BR112012024278A2 (pt) * 2010-03-25 2016-05-24 Sanofi Aventis Deutschland módulo medicamentoso acoplável a um dispositivo de entrega de medicamentos e sistema de administração de medicamentos
US8496619B2 (en) 2011-07-15 2013-07-30 Antares Pharma, Inc. Injection device with cammed ram assembly
US9220660B2 (en) 2011-07-15 2015-12-29 Antares Pharma, Inc. Liquid-transfer adapter beveled spike
US9486583B2 (en) 2012-03-06 2016-11-08 Antares Pharma, Inc. Prefilled syringe with breakaway force feature
EP2833944A4 (fr) 2012-04-06 2016-05-25 Antares Pharma Inc Administration par injection par jet assistée par une aiguille de compositions de testostérone
WO2013169804A1 (fr) 2012-05-07 2013-11-14 Antares Pharma, Inc. Dispositif d'injection par jet assisté par une aiguille, présentant une force de déclenchement réduite
WO2014124464A1 (fr) 2013-02-11 2014-08-14 Travanty Michael Dispositif d'injection à jet assistée par aiguille ayant une force de déclenchement réduite
CA2905031C (fr) 2013-03-11 2018-01-23 Hans PFLAUMER Injecteur de dose avec systeme a pignon
US9199037B2 (en) * 2013-03-15 2015-12-01 Windgap Medical, Inc. Portable drug mixing and delivery system and method
WO2016067179A1 (fr) 2014-10-29 2016-05-06 Wockhardt Limited Dispositif d'administration de médicament pour l'administration de deux doses multiples ou plus de médicaments, indépendamment sélectionnables par l'utilisateur avec des mécanismes de verrouillage de dose variable actionnable par l'utilisateur
CN107847681A (zh) * 2015-08-19 2018-03-27 卡贝欧洲有限公司 药物输送装置
EP3930794A1 (fr) * 2017-11-21 2022-01-05 Sanofi Récipient pour au moins un premier médicament injectable et dispositif d'injection
EP3810230A4 (fr) * 2018-06-20 2022-03-23 Koska Family Ltd. Systèmes et méthodes d'administration d'agent médicamenteux à deux constituants

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US3563240A (en) * 1966-07-20 1971-02-16 Jules Silver Dual unit syringe
US3908654A (en) * 1974-08-02 1975-09-30 Rit Rech Ind Therapeut Dispensing package for a dry biological and a liquid diluent
US5281198A (en) * 1992-05-04 1994-01-25 Habley Medical Technology Corporation Pharmaceutical component-mixing delivery assembly
US20020007142A1 (en) * 2000-05-22 2002-01-17 Birger Hjertman Medical arrangement
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WO2019211858A1 (fr) * 2018-05-04 2019-11-07 Sealantis Ltd. Système de reconstitution et de mélange

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CN102458519A (zh) 2012-05-16
CA2763506A1 (fr) 2010-12-09
CN102458519B (zh) 2014-05-21
IL216571A0 (en) 2012-03-01
US20120116349A1 (en) 2012-05-10
US9089648B2 (en) 2015-07-28
BRPI1012572A2 (pt) 2016-03-29
AU2010255755B2 (en) 2014-12-11
EP2437809A1 (fr) 2012-04-11
IL216571A (en) 2015-05-31
JP2012528636A (ja) 2012-11-15
JP5887263B2 (ja) 2016-03-16
AR076716A1 (es) 2011-06-29
TW201103594A (en) 2011-02-01
AU2010255755A1 (en) 2011-12-22

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